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https://www.readbyqxmd.com/read/28088086/design-and-synthesis-of-new-raf-kinase-inhibiting-antiproliferative-quinoline-derivatives-part-2-diarylurea-derivatives
#1
Mohammed I El-Gamal, Mohammad Ashrafuddin Khan, Hamadeh Tarazi, Mohammed S Abdel-Maksoud, Mahmoud M Gamal El-Din, Kyung Ho Yoo, Chang-Hyun Oh
This article describes the design, synthesis, and biological screening of a new series of diarylurea derivatives possessing quinoline nucleus. Nine target compounds were selected by the National Cancer Institute (NCI, Bethesda, Maryland, USA) for in vitro antiproliferative screening against a panel of 58 cancer cell lines of nine cancer types. Following one-dose initial screening, compounds 1d-g and 2b were selected for 5-dose screening in order to calculate their IC50 and total growth inhibition (TGI) values against the cell lines...
January 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28088038/evidence-of-functional-duplicity-of-nestin-expression-in-the-adult-mouse-midbrain
#2
Parisa Farzanehfar, Shi Sheng Lu, Anupa Dey, Dharshani Musiienko, Hamzah Baagil, Malcolm K Horne, Tim D Aumann
Whether or not neurogenesis occurs in the adult substantia nigra pars compacta (SNc) is an important question relevant for developing better treatments for the motor symptoms of Parkinson's disease (PD). Although controversial, it is generally believed that dividing cells here remain undifferentiated or differentiate into glia, not neurons. However, there is a suggestion that Nestin-expressing neural precursor cells (NPCs) in the adult SNc have a propensity to differentiate into neurons, which we sought to confirm in the present study...
January 5, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28088016/release-and-cytotoxicity-studies-of-magnetite-ag-antibiotic-nanoparticles-an-interdependent-relationship
#3
Olena Ivashchenko, Anna Woźniak, Emerson Coy, Barbara Peplinska, Jacek Gapinski, Stefan Jurga
Though the cytotoxic properties of magnetite nanoparticles (NPs) are rather well investigated and known to be dose dependent and rather low, surface functionalization can drastically change their properties. To determine whether the cytotoxicity of magnetite/Ag/antibiotic NPs may be associated, among other things, with iron, silver and antibiotic release, this study investigates the release profiles and cytotoxicity of magnetite/Ag/rifampicin and magnetite/Ag/doxycycline NPs compares it similar profiles from magnetite, magnetite/Ag NPs and antibiotics...
January 9, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28088012/new-4-4-chlorophenyl-2-2-6-2%C3%A2-terpyridine-ruthenium-ii-complexes-synthesis-characterization-interaction-with-dna-bsa-and-cytotoxicity-studies
#4
Milan M Milutinović, Ana Rilak, Ioannis Bratsos, Olivera Klisurić, Milan Vraneš, Nevenka Gligorijević, Siniša Radulović, Živadin D Bugarčić
In this study, we have developed a series of new monofunctional Ru(II) complexes of the general formula mer-[Ru(Cl-Ph-tpy)(N-N)Cl]Cl in which Cl-Ph-tpy is 4'-(4-chlorophenyl)-2,2':6',2″-terpyridine, N-N is a bidentate chelating ligand (1,2-diaminoethane (en, 1), 1,2-diaminocyclohexane (dach, 2) or 2,2'-bipyridine (bpy, 3)). All complexes were fully characterized by elemental analysis and spectroscopic techniques (IR, UV-Vis, 1D and 2D NMR). Their chemical behavior in aqueous solution was studied by UV-Vis and NMR spectroscopy showing that all compounds are relatively labile leading to the formation of the corresponding aqua species 1aq-3aq...
October 14, 2016: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28088004/a-catechin-nanoformulation-inhibits-wm266-melanoma-cell-proliferation-migration-and-associated-neo-angiogenesis
#5
Nicoletta di Leo, Matteo Battaglini, Liron Berger, Martina Giannaccini, Luciana Dente, Silke Hampel, Orazio Vittorio, Giuseppe Cirillo, Vittoria Raffa
We validated the anticancer potential of a nanoformulation made by (+)-catechin, gelatin and carbon nanotubes in terms of inhibition of cancer cell proliferation, migration and associated neo-angiogenesis. Gelatin was selected to stabilize the catechin without compromising its anti-oxidant potential and the carbon nanotubes were used to increase its intracellular bioavailability. The anticancer potential of the resulting nanohybrid was validated on an aggressive melanoma cell line, in vitro and in zebrafish xenotransplants...
January 11, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28087946/invasion-of-host-cells-and-tissues-by-uropathogenic-bacteria
#6
Adam J Lewis, Amanda C Richards, Matthew A Mulvey
Within the mammalian urinary tract uropathogenic bacteria face many challenges, including the shearing flow of urine, numerous antibacterial molecules, the bactericidal effects of phagocytes, and a scarcity of nutrients. These problems may be circumvented in part by the ability of uropathogenic Escherichia coli and several other uropathogens to invade the epithelial cells that line the urinary tract. By entering host cells, uropathogens can gain access to additional nutrients and protection from both host defenses and antibiotic treatments...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087941/interplay-between-myeloid-cells-and-humoral-innate-immunity
#7
Sébastien Jaillon, Eduardo Bonavita, Cecilia Garlanda, Alberto Mantovani
The innate immune system represents the first line of defense against pathogens and comprises both a cellular and a humoral arm. Fluid-phase pattern recognition molecules (PRMs), which include collectins, ficolins, and pentraxins, are key components of the humoral arm of innate immunity and are expressed by a variety of cells, including myeloid, epithelial, and endothelial cells, mainly in response to infectious and inflammatory conditions. Soluble PRMs share basic multifunctional properties including activation and regulation of the complement cascade, opsonization of pathogens and apoptotic cells, regulation of leukocyte extravasation, and fine-tuning of inflammation...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087810/akt1-lkb1-and-yap1-revealed-as-myc-interactors-with-nanoluc-based-protein-fragment-complementation-assay
#8
Xiu-Lei Mo, Qi Qi, Andrei A Ivanov, Qiankun Niu, Yin Luo, Jonathan Havel, Russell Goetze, Sydney Bell, Carlos S Moreno, Lee A D Cooper, Margaret A Johns, Fadlo R Khuri, Yuhong Du, Haian Fu
The c-Myc (MYC) transcription factor is a major cancer driver and a well-validated therapeutic target. However, directly targeting MYC has been challenging. Thus, identifying proteins that interact with and regulate MYC may provide alternative strategies to inhibit its oncogenic activity. Here we report the development of a NanoLuc®-based protein-fragment complementation assay (NanoPCA) and mapping of the MYC protein interaction hub in live mammalian cells. The NanoPCA system was configured to enable detection of protein-protein interactions (PPI) at the endogenous level, as shown with PRAS40 dimerization, and detection of weak interactions, such as PINCH1-NCK2...
January 13, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28087808/identification-of-a-novel-liver-x-receptor-agonist-that-regulates-the-expression-of-key-cholesterol-homeostasis-genes-with-distinct-pharmacological-characteristics
#9
Ni Li, Xiao Wang, Yanni Xu, Yuan Lin, Ningyu Zhu, Peng Liu, Duo Lu, Shuyi Si
Activation of Liver X receptor (LXR) is associated with cholesterol metabolism and anti-inflammatory processes, which makes beneficial to anti-atherosclerosis. Nevertheless, existing agonists which target LXR, for example TO901317, are related to unwanted side-effects. In the present study, using a screening method we identified IMB-808, which displayed potent dual LXRα/β agonistic activity. In vitro, IMB-808 effectively increased the expressing quantity of genes related to reverse cholesterol transport process as well as those associated with cholesterol metabolism pathway in multiple cell lines...
January 13, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28087766/control-of-amygdala-circuits-by-5-ht-neurons-via-5-ht-and-glutamate-co-transmission
#10
Ayesha Sengupta, Marco Bocchio, David M Bannerman, Trevor Sharp, Marco Capogna
: The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Thus, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin (ChR2) genetically targeted to 5-HT neurons...
January 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28087752/deficient-retinoid-driven-angiogenesis-may-contribute-to-failure-of-adult-human-lung-regeneration-in-emphysema
#11
John-Poul Ng-Blichfeldt, Joana Alçada, M Angeles Montero, Charlotte H Dean, Uta Griesenbach, Mark J Griffiths, Matthew Hind
BACKGROUND: Molecular pathways that regulate alveolar development and adult repair represent potential therapeutic targets for emphysema. Signalling via retinoic acid (RA), derived from vitamin A, is required for mammalian alveologenesis, and exogenous RA can induce alveolar regeneration in rodents. Little is known about RA signalling in the human lung and its potential role in lung disease. OBJECTIVES: To examine regulation of human alveolar epithelial and endothelial repair by RA, and characterise RA signalling in human emphysema...
January 13, 2017: Thorax
https://www.readbyqxmd.com/read/28087740/bone-microenvironment-changes-in-latexin-expression-promote-chemoresistance
#12
Mi Zhang, Mary Osisami, Jinlu Dai, Jill M Keller, June Escara-Wilke, Atsushi Mizokami, Evan T Keller
: Although docetaxel (DOX) is the standard of care for advanced prostate cancer (PCa), most patients develop resistance to DOX. Therefore, elucidating the mechanism that underlies resistance to DOX is critical to enhance therapeutic intervention. Mining cDNA microarray from the PC-3 PCa cell line and its DOX-resistant derivative (PC3-TxR) revealed decreased latexin (LXN) expression in the resistant cells. LXN expression was inversely correlated with taxane resistance in a panel of PCa cell lines...
January 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28087739/tnf-signaling-through-rip1-kinase-enhances-sn38-induced-death-in-colon-adenocarcinoma
#13
Lucia Cabal-Hierro, Peter J O'Dwyer
: Elucidation of tumor necrosis factor (TNF)-directed mechanisms for cell death induction and maintenance of tumor growth has revealed a role for receptor-interacting protein kinases 1 and 3 (RIPK1/RIP1 and RIPK3/RIP3), components of the necrosome complex, as determinants of cell fate. Here the participation of TNF signaling was analyzed with regard to the cytotoxic action of different DNA damaging agents in a panel of colon cancer cells. While most of these cell lines were insensitive to TNF, combination with these drugs increased sensitivity by inducing cell death and DNA damage, especially in the case of the topoisomerase inhibitor SN38...
January 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28087713/functional-genomics-reveals-that-tumors-with-activating-phosphoinositide-3-kinase-mutations-are-dependent-on-accelerated-protein-turnover
#14
Teresa Davoli, Kristen E Mengwasser, Jingjing Duan, Ting Chen, Camilla Christensen, Eric C Wooten, Anthony N Anselmo, Mamie Z Li, Kwok-Kin Wong, Kristopher T Kahle, Stephen J Elledge
Activating mutations in the phosphoinositide 3-kinase (PI3K) signaling pathway are frequently identified in cancer. To identify pathways that support PI3K oncogenesis, we performed a genome-wide RNAi screen in isogenic cell lines harboring wild-type or mutant PIK3CA to search for PI3K synthetic-lethal (SL) genes. A combined analysis of these results with a meta-analysis of two other large-scale RNAi screening data sets in PI3K mutant cancer cell lines converged on ribosomal protein translation and proteasomal protein degradation as critical nononcogene dependencies for PI3K-driven tumors...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28087695/novel-interconnections-in-lipid-metabolism-revealed-by-overexpression-of-sphingomyelin-synthase-1
#15
Gergana M Deevska, Patrick P Dotson, Alexander A Karakashian, Giorgis Isaac, Mark Wrona, Samuel B Kelly, Alfred H Merrill, Mariana N Nikolova-Karakashian
This study investigates the consequences of elevating sphingomyelin synthase 1 (SMS1) activity, which generates the main mammalian sphingolipid, sphingomyelin. HepG2 cells stably transfected with SMS1 (HepG2-SMS1), exhibit elevated enzyme activity in vitro and increased sphingomyelin content (mainly C22:0- and C24:0-sphingomyelin), but lower hexosylceramide (Hex-Cer) levels. HepG2-SMS1 cells have less triacylglycerols than controls but similar diacylglycerol acyltransferase activity, triacylglycerol secretion, and mitochondrial function...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28087659/plant-parasitic-nematodes-towards-understanding-molecular-players-in-stress-responses
#16
REVIEW
François-Xavier Gillet, Caroline Bournaud, Jose Dijair Antonino de Souza Júnior, Maria Fatima Grossi-de-Sa
BACKGROUND: Plant-parasitic nematode interactions occur within a vast molecular plant immunity network. Following initial contact with the host plant roots, plant-parasitic nematodes (PPNs) activate basal immune responses. Defence priming involves the release in the apoplast of toxic molecules derived from reactive species or secondary metabolism. In turn, PPNs must overcome the poisonous and stressful environment at the plant-nematode interface. The ability of PPNs to escape this first line of plant immunity is crucial and will determine its virulence...
January 13, 2017: Annals of Botany
https://www.readbyqxmd.com/read/28087650/simkania-negevensis-may-produce-long-lasting-infections-in-human-pneumocytes-and-endometrial-cells
#17
Manon Vouga, David Baud, Gilbert Greub
Simkania negevensis is a novel Chlamydia-related bacterium and the founding member of the Simkaniaceae family within the Chlamydiales order. Little is known about the biology and pathogenesis of this bacterium. So far, S. negevensis has been considered as an amoebal symbiont, but its natural host remains unknown. Moreover, evidence of human exposition has been reported worldwide and an association with pneumonia and bronchiolitis is suspected. Here, we evaluated the ability of S. negevensis to replicate in potential environmental reservoirs, namely amoebae and arthropods, as well as in mammalian cells (Vero cells, pneumocytes and endometrial cells) and further evaluated the characteristics of its replicative vacuole...
January 12, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28087642/stxbp4-drives-tumor-growth-and-is-associated-with-poor-prognosis-through-pdgf-receptor-signaling-in-lung-squamous-cell-carcinoma
#18
Yukihiro Otaka, Susumu Rokudai, Kyoichi Kaira, Michiru Fujieda, Ikuko Horikoshi, Reika Kawabata, Shinji Yoshiyama, Takehiko Yokobori, Yoichi Ohtaki, Kimihiro Shimizu, Tetsunari Oyama, Jun'ichi Tamura, Carol Prives, Masahiko Nishiyama
PURPOSE: Expression of the ΔN isoform of p63 (ΔNp63) is a diagnostic marker highly specific for lung squamous cell carcinoma (SCC). We previously found that Syntaxin Binding Protein 4 (STXBP4) regulates ΔNp63 ubiquitination, suggesting that STXBP4 may also be a SCC biomarker. To address this issue, we investigated the role of STXBP4 expression in SCC biology and the impact of STXBP4 expression on SCC prognosis. EXPERIMENTAL DESIGN: We carried out a clinicopathological analysis of STXBP4 expression in 87 lung SCC patients...
January 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28087632/sequential-organogenesis-sets-two-parallel-sensory-lines-in-medaka
#19
Ali Seleit, Isabel Krämer, Elizabeth Ambrosio, Nicolas Dross, Ulrike Engel, Lázaro Centanin
Animal organs are typically formed during embryogenesis by following one specific developmental programme. Here we report that neuromast organs are generated by two distinct and sequential programmes that result in parallel sensory lines in medaka embryos. A ventral posterior lateral line (pLL) is composed of neuromasts deposited by collectively migrating cells while a midline pLL is formed by individually migrating cells. Despite the variable number of neuromasts among embryos, the sequential programmes that we describe here fix an invariable ratio between ventral and midline neuromasts...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087600/sunitinib-stimulates-expression-of-vegfc-by-tumor-cells-and-promotes-lymphangiogenesis-in-clear-cell-renal-cell-carcinomas
#20
Maeva Dufies, Sandy Giuliano, Damien Ambrosetti, Audrey Claren, Papa Diogop Ndiaye, Michalis Mastri, Walid Moghrabi, Lindsay S Cooley, Marc Ettaiche, Emmanuel Chamorey, Julien Parola, Valerie Vial, Marilena Lupu-Plesu, Jean-Christophe Bernhard, Alain Ravaud, Delphine Borchiellini, Jean Marc Ferrero, Andreas Bikfalvi, John M L Ebos, Khalid S A Khabar, Renaud Grepin, Gilles Pagès
Sunitinib is an antiangiogenic therapy given as a first-line treatment for renal cell carcinoma (RCC). While treatment improves progression-free survival, most patients relapse. We hypothesized that patient relapse can stem from the development of a lymphatic network driven by the production of the main growth factor for lymphatic endothelial cells, vascular endothelial growth factor C (VEGFC). In this study, we found that sunitinib can stimulate VEGFC gene transcription and increase VEGFC mRNA half-life. Additionally, sunitinib activated p38 MAP kinase, which resulted in the upregulation/activity of HuR and inactivation of tristetraprolin, two AU-rich-element binding proteins...
January 13, 2017: Cancer Research
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